Chinese herbal medicines have been used historically in the treatment of alcohol and drug abuse. They are still prescribed in China and Southeast Asia, and their efficacy has been documented. We have shown that one of these remedies, NPI-028, will reduce alcohol intake in alcohol-preferring rats and monkeys. The goal of this Research Project 2 is to determine the efficacy of herbal remedies (NPI-028 and NPI-025) and fractions in animal models of craving and relapse. First we will test the remedies and compounds derived from Project 1 with kappa activity for efficacy in reducing voluntary alcohol intake in alcohol-preferring C57Bl mice (Aim 1). Because of its small size, this species will require only a small amount of compound. Any compound that reduces alcohol intake in mice will be tested for effects on the elevated alcohol intake associated with alcohol deprivation in P rats (Aim 2). This elevated intake is reminiscent of the binge drinking exhibited by the alcoholic upon resuming drinking. Compound will be administered either shortly before resumption of drinking to examine acute effects or during abstinence (deprivation) to examine long-term effects on relapse. In Aim 3, effects on the reinstatement of responding for alcohol will be determined. This protocol also involves a period of abstinence, so it will be possible to administer compound either during the abstinence phase or acutely just before reinstatement. Aim 4 will test for effects on cocaine discrimination in rats and monkeys to address the potential for treatment of cocaine addiction. Aims 1-3 will be carried out at the Center for Alcohol Study, University of North Carolina, and Aim 4 will be performed at McLean Hospital/Harvard Medical School. We believe that only those herbal remedies or compounds that withstand rigorous tests in sequential animal models are worthy of clinical trials designed to prevent relapse in alcohol and drug addiction.